1. Technical Field of the Invention
The invention relates a method of treatment of osteoarthritis pain. The method more particularly relates to the treatment of osteoarthritis pain by administration of a histamine H3 receptor antagonist, a salt thereof, or a composition comprising such compound or salt.
2. Description of Related Technology
Pain of various different types afflicts virtually all humans and animals at one time or another. A substantial number of medical disorders and conditions produce some sort of pain as a prominent concern requiring treatment. Pain is the one of the most common significant medical issues reported in the clinic and it affects the broadest group of patients. Distinct types and manifestations of pain are reported. Different pain types can be related to the origin of the pain, the underlying pathology, or different pharmacological agents that demonstrate efficacy (or lack thereof) in treating the pain.
The pain can be caused by different reasons. For example, the prominent causes of inflammatory pain are burns and chemical irritation. Post-surgical pain can arise after incisions of the skin and internal organs, among other conditions. Nerve damage can lead to neuropathic pain and neuropathy arising from sciatic nerve irritation, chronic diabetes, and chemotherapy. Osteoarthritis pain typically arises from a cause having physical origin, for example, such as the erosion of joint cartilage with a resulting mechanical irritation of the bones and joint.
Various types of pain are treated with distinct, different therapeutic agents. For example, acute inflammatory pain is typically treated with non-steroidal anti-inflammatory (NSAID) agents and cyclooxygenase inhibitors, for example aspirin or celecoxib. Post-surgical pain is typically treated with opiate receptor agonists, for example codeine. Neuropathic pain can be treated with anti-depressant agents and neurotransmitter reuptake inhibitors, for example duloxetine. Osteoarthritis pain is commonly treated with acetominophen.
A distinct type of pain where patients are not completely treatable by any of the currently available drugs or by agents is neuropathic pain. The drug duloxetine can usefully provide partial relief of this type of pain. Neuropathic pain can develop in response to previous injury or ongoing tissue injury, nerve injury, or diabetes. Neuropathic pain is distinct from other types of pain, for example inflammatory pain, in that it persists long after signs of the original injury or damage have disappeared. Neuropathic pain also is associated with allodynia, hyperalgesia, or causalgia (Dworkin Clinical Journal of Pain (2002) vol. 18(6) pp. 343-9). The topic and physiology of neuropathic pain has been reviewed in the scientific literature (Smith, et al. Drug Development Research (2001) vol. 54(3), pp. 140-153; Collins and Chessell Expert Opinion on Emerging Drugs (2005) vol. 10(1), pp. 95-108; Vinik and Mehrabyan Medical Clinics of North America (2004), vol. 88(4), pp. 947-999; Dray, Urban, and Dickenson Trends in Pharmacological Sciences (1994) vol. 15(6) pp. 190-7; Dworkin Clinical Journal of Pain (2002) vol. 18(6) pp. 343-9.) Some histamine H3 receptor antagonists have been reported to have efficacy in animal models of neuropathic pain (Medhurst, et al. Biochemical Pharmacology (2007) 73, pp. 1182-1194; Medhurst, et al. Pain (2008) 138, pp. 61-69).
A very wide variety of compounds with H3 receptor antagonist activity has been reported (Berlin and Boyce, Expert Opinion in Therapeutic Patents (2007) 17(6) pp. 675-687; Esbenshade, Browman, Bitner, Strakhova, Cowart, and Brioni, Br. J. Pharmacol. (2008), 154, pp. 1166-1181.) Different H3 antagonists have been found active in models of specific human diseases, including for example, Alzheimer's disease, age-related cognitive and memory impairment, attention-deficit hyperactivity disorder, cognitive disfunction related to schizophrenia, allergic rhinitis, and sleep disorders.
In contrast to neuropathic pain, pain from osteoarthritis is thought to arise first from some structural pathology, and then from damage or destruction of the cartilage and alteration of the joint surface. Consequent mechanical irritation of nerves in bones and joints leads to pathological sensitization of peripheral and central nerves (Dray and Read, Arthritis Research and Therapy (2007) 9, p. 212). The pain of osteoarthritis in the clinic is independent of ongoing inflammation (Fernihough, et al. Pain (2004) 112, pp. 83-93; Joshi and Honore, Expert Opinion in Drug Discovery (2006), 1(4), pp. 323-334). As yet, there is no pharmacological therapy that reverses the damage to the joint in osteoarthritis. As such, therapeutic agents of diverse pharmacological mechanisms are used to treat the pain symptoms of osteoarthritis. These agents are associated with either incomplete relief of pain or mechanism- and agent-based side effects that compromise the quality of the treatment (Rubin, Journal of the American Osteopathic Association (2005) 105, S23-S28; Dray and Read, Arthritis Research and Therapy (2007) 9, p. 212). As such, it would be particularly beneficial to identify new methods for treating osteoarthritis. It would be particularly beneficial if such methods are based on previously unexplored mechanisms for pain treatment that may offer improved pain relief or are less associated with side effects. However, no H3 antagonist has yet been reported to demonstrate effect in osteoarthritis pain.